论文部分内容阅读
γ-氨基丁酸是重要的抑制性神经传递物质,4-喹啉酮衍生物作用于GABA_A受体具有广泛的生物活性。本文采用DIS- COtech法构建大鼠GABA_A/BZ受体4-喹啉酮衍生物激动剂的药效团模型,同时根据分子骨架叠合规则构建CoMFA模型,模型的交叉验证系数为0.681,非交叉验证系数为0.967,药效团模型和CoMFA模型具有一致性。根据模型分析配体-受体间的相互作用,设计一系列化合物并预报了其活性,为设计高活性的化合物提供参考。
γ-Aminobutyric acid is an important inhibitory neurotransmitter, and 4-quinolinone derivatives have a wide range of biological activities on GABA_A receptors. In this paper, the pharmacophore model of rat GABA_A / BZ receptor 4-quinolinone derivative agonist was constructed by DIS-COtech method. At the same time, the CoMFA model was constructed according to the rules of molecular skeleton overlap. The cross validation coefficient of the model was 0.681, The validation coefficient is 0.967, and the pharmacophore model is consistent with the CoMFA model. Based on the model analysis of ligand-receptor interactions, a series of compounds were designed and their activities predicted, providing a reference for the design of highly active compounds.